Atorvastatin Tablets Finish Product Testing Procedure By UV and HPLC Method like any other pharmaceutical product, is a crucial part of ensuring their safety, efficacy, and quality. Here’s an overview of the typical testing procedures involved in the production and quality control of Atorvastatin tablets:
It’s essential to note that specific testing procedures may vary depending on the country, regulatory agency, and pharmaceutical company. Manufacturers must adhere to good manufacturing practices (GMP) to maintain the quality and consistency of their products.
The goal of these testing procedures is to ensure that Atorvastatin tablets are safe, effective, and of high quality, providing patients with the expected therapeutic benefits while minimizing risks and maintaining product consistency.
PURPOSE:
To describe the procedure for analysis at the in-process and finished stage of Atorvastatin Tablet.
SCOPE:
This SAP gives a detailed outline for the finished product analysis of the Atorvastatin Tablet and will cover process testing activities on a physical, chemical & instrumental basis.
RESPONSIBILITY:
QC Analyst is responsible for physical/chemical testing and preparing standard analytical procedures.
It is the responsibility of the QC Manager to assist and ensure the Testing Procedure as per SAP and to make certain that this SAP is followed in its entirety, reviewed regularly, and revised as necessary.
REFERENCE:
JAPANESE PHARMACOPOEIA
MATERIAL AND EQIUPMENT:
- UV Spectrophotometer
- HPLC
- Dissolution apparatus
- Friability apparatus
- Hardness apparatus
- Disintegration Tester
- Vernier Caliper
- Analytical Balance
- Moisture analyzer
- Mortar and pestle
- Spatula
- Filter Paper
- Magnetic Stirrer & Hot Plate
- Sonicator
- Vacuum Pump
- Glassware
- Methanol AR Grade
- Distilled water
PROCEDURE:
FINAL MIX
Description:
A White powder.
Procedure: Take 2.0 g of the test sample in a watch glass and observe visually with black background. Check the appearance of color, nature and any visible foreign particles.
Identification: (By UV SPECTROPHOTOMETER)
The spectrum of the sample preparation corresponds to spectrum of the standard preparation as obtained in the assay.
Loss on Drying: (By Moisture Analyzer)
Procedure:
Turn on instrument 20 minute before the test. Take 2 g powder spread uniformly on Moisture Analyzer plate. Close the lid and press start button.
NMT 5.0% when determined by LOD Apparatus, Use 2.0 g of powder.
Assay: (Limit: 95%-105%)Compression Weight of Powder/Tablet:………
Assay Procedure By HPLC:
Mobile Phase:
Buffer: Dissolve 10.5 g of citric acid monohydrate in 900 mL of water, adjust to pH 4.0 with ammonia solution, and add water to make 1000 mL.
Acetonitrile: Tetrahydrofuran: Buffer
270: 200 : 530
Diluent: Methanol: Water: 1:1
Standard Solution:
Take 43.4 mg of Atorvastatin Calcium Trihydrate WS equivalent to40 mg of atorvastatin dissolved in diluent and make up the volume to 50mL with diluent. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 2 mL from standard stock solution and make up the volume to 20 mL with diluent.
Sample solution:
Take compression weight of finally grinded granules equivalent to40 mg of atorvastatin and dissolved in diluent and make up the volume to 50mL with diluent. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 2 mL of filtrate to a 20mL volumetric flask make up volume with diluent.
Pass through a membrane filter of 0.45-µm pore size.
Chromatographic system
- Mode: LC
- Detector: UV 244 nm.
- Column: 4.6-mm x 25-cm; 5-µm packing L1
- Temperatures: Column: 30°C
- Flow rate: 1.0 mL/min
- Injection volume: 20 µL
System Suitability:
Samples: Standard solution
Tailing Factor: NMT 2.0
Relative standard deviation: NMT 1.0%
Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim x Factor
ALTERNATE ASSAY METHOD BY UV
Diluent:
Methanol : Water 1 : 1
Standard Solution:
Take 44 mg of Atorvastatin Calcium Trihydrate WS dissolved in methanol and make up the volume to 100mL with diluent. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 1 mL from standard stock solution and make up the volume to 100 mL with diluent.
Sample solution:
Take compression weight of finally grinded granules equivalent to 200mg atorvastatin and dissolved in 60mL of diluent, sonicate for 5 minutes and make up the volume to 100mL with diluent. Shake by mechanical mean for 5 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 1 mL of filtrate to a 100mL volumetric flask make up volume with diluent. Take reading at UV spectrophotometer at 245 nm using diluent as blank.
Calculations:
Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Absorbance x Sample Concentration x Label Claim x Factor
Limit: Atorvastatin (Calcium Trihydrate): 95%-105%of the labeled amount
Uniformity of Dosage Units: (By Weight Variation)
Weigh 20 tablets individually and calculate the average weight as:
Average weight = (Weight Of 20 Tablets)/20
Weigh all these tablets individually and mark among these weights maximum (WMax) & minimum (WMin) weight tablets. Calculate the maximum and minimum variation in percent as:
Maximum% age variation =((WMax) – (WAvg.))/WAvg×100
Minimum % age variation ((WMin) – (WAvg.))/WAvg×100
Hardness Test & Dimensions:
Perform the hardness test on 10 tablets and take the average. Power on the instrument and regulate zero adjustment and preset the ‘’HARDNESS’’ and “Thickness” mode. Place the tablet on the test plate, begin testing and read the hardness thickness and diameter. Clean the shattered tablet and print out test results, perform the test on 10 tablets and take the average.
Hardness Standard Limit:……
Thickness Standard Limit:……
Length/Diameter Standard Limit:…….
Friability Test:
For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum. Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before, and accurately weigh. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are doubtful or if the weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A maximum mean weight loss from the three samples of not more than 1.0% is considered acceptable for most products.
% FRIABILITY= W1-W2 x 100 / W1
Disintegration Test:
Place the beaker filled with water into the beaker stand inside the bath and. Switch on the instrument, set the temperature at 37ºC± 2º C and wait till the temperature of the beaker reaches to the 37ºC± 2º C. Engage the basket on basket hook put the tablets in 6 tubes individually and place the discs then start the oscillations and timer. Note the disintegration time of all the six tablets.
Note: the Disintegration time of 1st tablet to the last tablet.
Disintegration Time: NMT 15 minutes at 370C ± 20C
Acceptance criteria of disintegration for tablets:
If 1 or 2 tablets fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the totals of 18 tablets tested disintegrate completely.
Dissolution Test:
USP Apparatus: USP Apparatus II Peddle
Medium: 900mL water
Speed: 75 rpm
Time: 30 Minute
Medium Temperature: 37º ± 0.5º
Recommended Sampling Time: Atorvastatin: 30 Minute
Diluent: Dissolution medium
Standard solution: 0.0222mg/ml of Atorvastatin (Calcium trihydrate) in medium.
Take 30.1 mg Atorvastatin calcium trihydrate WS equivalent to 27.77 mg of Atorvastatin in 50mL volumetric flask add 5 mL methanol to dissolve atorvastatin then make up volume with medium.
Take 2 mL from standard stock solution and make up the volume up to 25 mL with medium.
Sample solution: Pass a portion of solution under through a suitable filter of 0.45-um pore size.
Instrumental Conditions
Mode: UV
Analytical wavelength: UV 241 nm
Blank: Medium
Calculations:
Sample Absorbance x Standard Concentration x Potency
Standard Absorbance x Sample Concentration x Factor
Tolerance:
The amount of drug dissolve in solution for each tablet is not less Than 80% of the amount stated on the label for Atorvastatin at 30 minutes.
Leak Test:
Take 06 blisters of tablet 03 filled and 03 empty. Dip these blisters in the bowl of leak test apparatus containing colored water. Create vacuum 250 mmHg and hold for one minute. Release vacuum and check the penetration of water inside the blisters. All blisters should be free of water.